Our existing colony of carcinogen-treated beagles, some with histologically proven lung cancer and others at high risk, will be serially studied. New dogs will be added. Our objective is to refine our model for surgical research. We seek that: (a) the primary occurs at a localized (pre-selected) site, (b) the biologic behavior resembles human epidermoid cancer, and (c) the evolution permits serial study of normal-to-neoplastic transitions in a predictable pattern. Cytogenetic and hormonal correlates of the neoplastic transition will be concomitantly assessed. Inbred beagles will have the proven carcinogenic method of frequent endobronchial submucosal injections of Benzo(a)pyrene and topical applications of N-methyl-nitrosourea. After preliminary hamster studies, other groups of beagles will receive endobronchial or parenchymal sustained release implants of either Dimethylbenzanthracene or Methylcholathrene. At later frequent bronchoscopic examinations, serial biopsies will be done and exfoliated cells obtained for cytologic and cytogenetic examination. Alveolar lavage methods for assessing peripheral lung lesions will be tested using a tracheal divider. We seek to determine the association between polyploidy and lung cancer and atypia, separating the polyploid cells with a Facs IV cell sorter. Separated cells will be grown in tissue culture. Tissue and blood specimens will be assayed for ACTH and beta-lipoprotein contend as hormonal markers of lung cancer. Additional hormonal studies will determine the precursors and forms of ACTH present, assess in vivo hormone production during carcinogenesis, and evaluate steroid responsiveness of ectopic peptide secretion.